Arrhythmogenesis in Brugada Syndrome: Role of Ventricular Structure

Brugada syndrome is a genetic disorder that results in decreased expression of cardiac Na+ channels, leading to abnormal electrical activity with onset in the right ventricle (RV). Given that INa is reduced globally, it remains unclear why the RV is more susceptible to arrhythmogenesis. This study tests the hypothesis that differences in geometry between left ventricle (LV) and RV promote altered conduction patterns under reduced INa. Using a 3D rabbit ventricular model that incorporates realistic geometry, simulations were performed where INa maximal conductance was varied from 60 to 100% of the normal level. Reentry was induced via diastolic stimulation of the LV or RV epicardium. Sustained reentry developed only at the 60% INa level for RV stimulation, while no reentry was induced for the LV regardless of INa levels. Activation map (figure) for the 60% INa model shows conduction block at the RV insertion region, where the safety factor (the ratio of total intracellular current vs. current needed to excite the cell) was zero. Propagation from the thin RV has insufficient current to excite tissue in the septum/LV, resulting in source-sink mismatch and block, thus predisposing the RV to arrhythmogenesis under reduced INa.View Large Image | View Hi-Res Image | Download PowerPoint Slide